Expression of delta-like protein 3 is reproducibly present in a subset of small cell lung carcinomas and pulmonary carcinoid tumors

Xie, Hao; Boland, Jennifer M.; Maleszewski, Joseph J.; Aubry, Marie Christine; Yi, Eunhee S.; Jenkins, Sarah M.; Koepplin, Justin W.; Terra, Simone; Mansfield, Aaron S.; Roden, Anja C.

doi:10.1016/j.lungcan.2019.07.016

Cited by 21 publications

(22 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…16 DLL3 is now a promising target of HGNEC, and DLL3 targeting agents are in development. 18 Rovapituzumab tesirine (Rova-T), a DLL3-targeted antibody conjugate, showed encouraging single-agent antitumor activity in patients with recurrent HGNEC in a phase 1 clinical trial. 17 In this trial, DLL3 expression was a strong predictor of the efficacy of Rova-T, and 35% of patients with DLL3 expression-positive HGNEC had an objective response, whereas 0% of patients with DLL3 expression-negative HGNEC had an objective response.…”

Section: Discussionmentioning

confidence: 99%

“…16 DLL3 is now considered a promising target of HGNEC, and DLL3-targeting agents are in development. 17,18 George et al reported that pulmonary LCNEC comprise two genomic subgroups with specific transcriptional patterns, defined as "type I LCNEC" and "type II LCNEC" in the first comprehensive molecular analysis of LCNEC. 1 In that article, type I LCNEC showed higher expression of neuroendocrine genes, as well as of DLL3, and the downregulation of Notch pathway genes.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

DLL3 expression is a predictive marker of sensitivity to adjuvant chemotherapy for pulmonary LCNEC

et al. 2020

View full text Add to dashboard Cite

Background The mammalian Notch family ligands delta‐like 3 (DLL3) is reported to be a potential therapeutic target for large cell neuroendocrine carcinomas (LCNEC). The effect of DLL3 expression on LCNEC prognosis has not yet been elucidated. Methods We reviewed the medical records of 70 LCNEC patients undergoing surgical resection between 2001 and 2015 using a prospectively maintained database. We performed immunohistochemistry for DLL3 and investigated the correlation between the sensitivity of LCNEC to platinum‐based adjuvant chemotherapy. Results DLL3 expression was positive in 26 (37.1%) LCNEC patients. A total of 23 patients (32.9%) received platinum‐based adjuvant chemotherapy. Among patients with DLL3 expression‐positive tumors, no difference was found in the five‐year overall survival (OS) or recurrence‐free survival (RFS) between patients with and without adjuvant chemotherapy (surgery + chemotherapy vs. surgery alone, five‐year OS: 58.3% vs. 35.7% P = 0.36, five‐year RFS: 41.7% vs. 35.7% P = 0.74). In contrast, among patients with DLL3‐negative tumors, significantly greater five‐year OS and RFS rates were observed for patients with adjuvant chemotherapy than for those without it (surgery + chemotherapy vs. surgery alone: five‐year OS: 90.0% vs. 26.9% P<0.01, five‐year RFS: 80.0% vs. 21.7% P < 0.01). A multivariate analysis for the RFS revealed that adjuvant chemotherapy was a significant independent prognostic factor among patients with DLL3‐negative tumors (hazard ratio [HR]: 0.05, 95% confidence interval [CI]: 0.01–0.41, P < 0.01), although it was not a factor among patients with DLL3‐positive tumors (HR: 0.73, 95% CI: 0.23–2.27, P = 0.58). Conclusions Our results revealed that DLL3 is a predictive marker of sensitivity to platinum‐based adjuvant chemotherapy for LCNEC. Key points Significant findings of the study DLL3 was a predictive marker of sensitivity to platinum‐based adjuvant chemotherapy for LCNEC. Among patients with DLL3 expression‐negative LCNEC, platinum‐based adjuvant chemotherapy significantly improved the OS and RFS, although it did not do so among patients with DLL3 expression‐positive LCNEC. What this study adds Our results suggest that DLL3 expression‐positive LCNEC may be better treated with other types of adjuvant chemotherapy, such as the anti‐DLL3 therapies if these effects are confirmed by ongoing clinical research.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DLL3 expression is a predictive marker of sensitivity to adjuvant chemotherapy for pulmonary LCNEC

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Finally, we were left with 16 eligible studies after screening the full text, among which 6 articles were included in our final analysis ( Fig. 1) [20][21][22][23][24][25]. Ten articles were excluded for the following reasons: seven articles were review researches and commentaries, one article did not report hazard ratios and Kaplan-Meier curves and 2 articles were abstracts and did not report relevant outcomes.…”

Section: Resultsmentioning

confidence: 99%

“…One interpretation of this result was that DLL3 expression varies between different populations. The American study indicated that the high expression of DLL3 was a marker of good prognosis [21], and there was no significant correlation between DLL3 expression and prognosis in several Japan studies [22,25], while the high expression of DLL3 is a marker of poor prognosis in China studies [20,23]. These results showed that the expression of DLL3 might be different in different populations.…”

Section: Discussionmentioning

confidence: 96%

“…Different antibodies and different cut-off values for DLL3 expression were employed in all the included studies and thus could also be another cause of the differences in results. The American study also explained their different results by claiming that many of the other studies were performed using mRNA expression instead of protein expression or used different cut-offs value of DLL3 expression [21].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Potential prognostic value of delta-like protein 3 in small cell lung cancer: a meta-analysis

Chen

Liu

et al. 2020

World J Surg Onc

View full text Add to dashboard Cite

Background: Current researches have revealed that delta-like protein 3 (DLL3) may be related with prognosis in patients with small cell lung cancer (SCLC). However, this finding remains controversial in small cell lung cancer. This meta-analysis was systematically performed to evaluate the prognostic value of DLL3 in SCLC. Methods: The PubMed, EMBASE and Web of Science databases were retrieved to collect the eligible references. Through Stata 15.0 software, we pooled hazard ratios (HR) with 95% confidence intervals (CI) by using random or fixed-effects models to evaluate the association between DLL3 and SCLC survival results. Results: A total of 6 interrelated studies including 645 patients were qualified. After we removed 1 study, the remaining 5 studies including 601 patients were pooled to testify that high expression of DLL3 was an inferior prognostic for patients with SCLC in Asian populations (HR = 1.37, 95% CI = 1.05, 1.69; I 2 = 0.0%, p = 0.000). The pooled results showed that DLL3 might be higher expression in advanced metastasis SCLC in Asian populations (RR = 0.84, 95% CI = 0.71, 0.99; I 2 = 44.7%, p = 0.039). But the expression of DLL3 was not correlated with sex (RR = 1.33, 95% CI = 0.98, 1.80; I 2 = 0.0%, p = 0.064), smoking history (RR = 1.01, 95% CI = 0.58, 1.75; I 2 = 72.1%, p = 0.967) and tumour stage (RR = 0.68, 95% CI = 0.44, 1.05; I 2 = 66.6%, p = 0.081). Conclusions: Our meta-analysis confirms that in Asian populations, high expression of DLL3 was a potential poor prognostic biomarker for SCLC and DLL3 highly expressed in advanced stage SCLC in Asian populations.

show abstract

Systematic Literature Review of the Prevalence and Prognostic Value of Delta-Like Ligand 3 Protein Expression in Small Cell Lung Cancer

Bylsma,

Pundole,

et al. 2023

Targ Oncol

View full text Add to dashboard Cite

Expression of delta-like protein 3 is reproducibly present in a subset of small cell lung carcinomas and pulmonary carcinoid tumors

Cited by 21 publications

References 18 publications

DLL3 expression is a predictive marker of sensitivity to adjuvant chemotherapy for pulmonary LCNEC

DLL3 expression is a predictive marker of sensitivity to adjuvant chemotherapy for pulmonary LCNEC

Potential prognostic value of delta-like protein 3 in small cell lung cancer: a meta-analysis

Systematic Literature Review of the Prevalence and Prognostic Value of Delta-Like Ligand 3 Protein Expression in Small Cell Lung Cancer

Contact Info

Product

Resources

About